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S1
Supplementary Information
Regiodivergent Reductive Coupling of 2-Substituted Dienes to Formaldehyde Employing
Ruthenium or Nickel Catalysts: Hydrohydroxymethylation via Transfer Hydrogenation
Alexander Köpfer,a Brannon Sam,
b Bernhard Breit
a* and Michael J. Krische
b*
aAlbert-Ludwigs-Universität Freiburg, Institut für Organische Chemie und Biochemie, 79104
Freiburg, Germany bUniversity of Texas at Austin, Department of Chemistry and Biochemistry, Austin, TX 78712,
USA
Table of Contents
I. General Experimental Details S2
II. Experimental Procedures and Spectroscopic Data for Novel Diene Substrates S3
III. Experimental Procedure and Spectroscopic Data for Nickel Couplings at C1 S11
IV. Experimental Procedure and Spectroscopic Data for Ruthenium Couplings at C2 S35
V. Experimental Procedure and Spectroscopic Data for Ruthenium Couplings at C3 S47
VI Experimental Procedure and Spectroscopic Data for Nickel Couplings at C4 S71
VII. Experimental Procedure and Spectroscopic Data for the Hiyama Coupling of the C4
Product.
S78
VIII. Deuterium Labeling for Nickel Coupling at C1 S80
IX. Deuterium Labeling for Ruthenium Coupling at C3 S82
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I. General Experimental Details.
All reactions were run under an atmosphere of argon, unless otherwise indicated. Anhydrous
solvents were transferred via oven-dried syringe. Reaction tubes were oven-dried and cooled
under a stream of argon. Reactions tubes were purchased from Fischer Scientific (catalog
number 14-959-35C). Toluene and 1,4-dioxanes were purified from sodium and benzophenone.
RuHCl(CO)(PPh3)3was prepared according to literature procedure.1 Ni(COD)2 and all ligands
were used as received from Strem Chemicals Inc. Isopropanol (99.8%, extra dry) and
paraformaldehyde were obtained and used as received from Acros Organics. For nickel catalysis,
paraformaldehyde was purchased and immediately taken into the drybox, where it was stored in
the refrigerator. Ni(COD)2, PCy3, and Cs2CO3 were purchased from Aldrich and stored in the
drybox prior to use. Unless noted otherwise, 2-substituted dienes 1-14 were prepared in
accordance with literature procedure.2 Analytical thin-layer chromatography (TLC) was carried
out using 0.25 mm commercial silica gel plates (Dynamic Adsorbents F254) and products were
visualized by UV, KMnO4 and/or anisaldehyde stain. Preparative column chromatography
employing Silicycle silica gel (40-63 μm) was performed according to the method of Still.3
Infrared spectra were recorded on a Perkin-Elmer 1600 spectrometer. High-resolution mass
spectra (HRMS) were obtained on a Karatos MS9 and are reported as m/z (relative intensity).
Accurate masses are reported for the molecular ion [M+H]+ or a suitable fragment ion. Proton
nuclear magnetic resonance (1H NMR) spectra were recorded with a Varian Gemini (400 MHz)
spectrometer. Chemical shifts are reported in delta (δ) units, parts per million (ppm) downfield
from tetramethylsilane or ppm relative to the center of the singlet at 7.26 ppm for
deuteriochloroform. Coupling constants are reported in Hertz (Hz). Carbon-13 nuclear magnetic
resonance (13
C NMR) spectra were recorded with a Varian Gemini or 400 (100 MHz)
spectrometer. Chemical shifts are reported in delta (δ) units, ppm relative to the center of the
triplet at 77.0 ppm for deuteriochloroform. 13
C NMR spectra were routinely run with broadband
decoupling. Fluorine-19 nuclear magnetic resonance (19
F NMR) spectra were recorded with a
Varian Gemini or 400 (100 MHz) spectrometer. Deuterium nuclear magnetic resonance
(2H NMR) spectra were recorded in CHCl3 solution with a Varian Gemini 500 (77 MHz)
spectrometer (relaxation delay 2.00 s).
1T. Joseph, S. S. Deshpande, S.B. Halligudi, A. Vinu, S. Ernst and M. Hartmann, J. Mol. Catal.A., 2003, 206, 13. 2 (a) K. Tonogaki and M. Mori, Tetrahedron Lett., 2002, 43, 2235; (b) W.Huang, Q. Shen, J. Wang, X. Zhou, J.
Org. Chem., 2008, 73, 1586; (c) T. Smejkal, H. Han, B. Breit and M. J. Krische, J. Am. Chem. Soc., 2009, 131,
10366; (d) R. R. Pidaparthi, C. S. Junker, M. E. Welker, C. S. Day and M. W. Wright, J. Org. Chem., 2009, 74,
8290; (e) E. Wada, S. Kanemasa, I. Fujiwara and O. Tsuge, Bull. Chem. Soc. Jpn., 1985, 58, 1942. 3W. C. Still, M. Kahn and A. Mitra, J. Org. Chem., 1978, 43, 2923.
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II. Experimental Procedures and Spectroscopic Data for Novel Dienes
1-(buta-1,3-dien-2-yl)-4-methylbenzene (2)
1-(buta-1,3-dien-2-yl)-4-methylbenzene (2) was prepared by modifying an enyne metathesis
method reported by Mori.4
A 100 mL round-bottom flask was charged with Grubb’s 2nd
generation catalyst (85 mg,
0.10 mmol, 2 mol%), 4-tolylacetylene (0.63 mL, 5.0 mmol, 100 mol%), and toluene (50 mL,
0.1 M). The reaction vessel was purged with ethylene gas followed by heating to 80 °C under 1
atm of ethylene gas. The reaction mixture was allowed to stir for 6 h at 80 °C and cooled to
ambient temperature. Ethyl vinyl ether (several drops) was added and the solvent was removed
in vacuo. The residue was purified by flash column chromatography (SiO2, 2% EtOAc/hexane)
to afford the title compound (0.50 g, 70%) as a colorless liquid.
1H NMR(400 MHz, CDCl3): δ 7.27 – 7.21 (m, 2H), 7.20 – 7.12 (m, 2H), 6.68 – 6.56 (m, 1H),
5.30 – 5.26 (m, 1H), 5.26 – 5.21 (m, 1H), 5.21 – 5.17 (m, 2H), 2.37 (s, 3H).
13
C NMR(100 MHz, CDCl3): 148.1, 138.2, 137.2, 136.8, 128.8, 128.1, 117.0, 116.4, 21.2.
HRMS (CI) Calcd. For C11H12 [M]+: 144.0937, Found: 144.0937.
FTIR (in CDCl3): 3087, 3026, 2921, 1512, 1437, 1379, 1020, 991, 893, 823, 729, 695 cm-1
.
4K. Tonogaki and M. Mori, Tetrahedron Lett., 2002, 43, 2235.
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1-(buta-1,3-dien-2-yl)-4-fluorobenzene (6)
1-(buta-1,3-dien-2-yl)-4-fluorobenzene (6) was prepared by modifying a nickel catalyzed
coupling method reported by Kumada.5
To a 300 mL sealed tube (sealing was used to prevent loss of chloroprene) equipped with a
magnetic stir bar was added Ni(dppe)Cl2 (0.26 g, 0.50 mmol,
1 mol%), Et2O (10 ml) and then chloroprene (6.6 g, 75 mmol, 1.5 equiv.). The mixture was
cooled to 0 °C and stirred for 5 min. Then 4-fluorophenylmagnesiumbromide6 (100 mL,
50 mmol, 0.5 M in Et2O) was added drop-wise under inert atmosphere followed by addition of
toluene (10 mL). The reaction mixture was allowed to warm to room temperature and stirred for
40 h. The reaction mixture was quenched with a saturated aqueous solution of NH4Cl (50 mL).
The aqueous layer was separated and extracted with Et2O (3 × 20 mL). The combined organic
phases were washed with brine (20 mL) and dried (Na2SO4). After evaporation of the solvents,
the mixture was purified by distillation (5 Torr, 50 °C) to furnish the title compound (3.5 g, 47%)
as a colorless liquid.
1H NMR (400 MHz, CDCl3): δ 7.34 – 7.23 (m, 2H), 7.09 – 6.99 (m, 2H),
6.61 (ddd, J = 17.2, 10.7, 0.6 Hz, 1H), 5.32 – 5.27 (m, 1H), 5.23 (ddd, J = 10.7, 1.2, 0.6 Hz, 1H),
5.20 – 5.11 (m, 2H).
13
C NMR (100 MHz, CDCl3): 162.3 (d, J = 245.9 Hz), 147.2, 138.1, 135.6 (d, J = 3.2 Hz, 2C),
129.9 (d, J = 8.0 Hz), 117.2, 117.1, 115.0 (d, J = 21.5 Hz, 2C).
19
F NMR (376 MHz, CDCl3): δ -115.17 (mc).
HRMS (CI) Calcd. For C10H8F [M]+: 148.0688, Found: 148.0689.
FTIR (in CDCl3): 3091, 2970, 1738, 1604, 1507, 1366, 1317, 1296, 1220, 1158, 1095, 1037,
1014, 991, 899, 838, 818, 735, 663 cm-1
.
5 K. Tamao, K. Sumitani, Y. Kiso, M. Zembayashi, A. Fujioka, S. Kodama, I. Nakajima, A. Minato and M.
Kumada, Bull. Chem. Soc. Japan., 1976, 49, 1958. 6 Prepared from 1-bromo-4-fluorobenzene and Mg in Et2O.
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(5-methylenehept-6-en-1-yl)benzene (9)
(5-methylenehept-6-en-1-yl)benzene (9) was prepared by modifying an iron catalyzed coupling
method reported by Cossy.7
To a flame dried one neck round bottom flask equipped with a magnetic stir bar was added FeCl3
(0.49 mg, 3.0 mmol, 20 mol%) and THF (50 ml). It was cooled to 0 °C followed by addition of
1-iodo-4-phenylbutane8 (3.9 g, 15 mmol, 1.0 equiv.) The resulting solution was stirred at 0 °C
for 10 min and a solution of chloroprene Grignard2d
(43 ml, 30 mmol, 0.7 M in THF, 2.0 equiv.)
and TMEDA (4.3 ml, 29 mmol, 1.9 equiv.) was added
drop-wise over 1 h. After further 2 h at 0 °C, the reaction mixture was quenched by adding an
aqueous saturated NH4Cl solution. After extractive workup and evaporation of the solvent, the
residue was purified by flash column chromatography (SiO2, 100% hexane) to furnish the title
compound (1.5 g, 53%) as a colorless liquid.
1H NMR (400 MHz, CDCl3): δ 7.29 – 7.23 (m, 2H), 7.19 – 7.13 (m, 3H),
6.35 (dd, J = 17.6, 10.8 Hz, 1H), 5.20 (ddd, J = 17.6, 1.1, 0.5 Hz, 1H), 5.07 – 4.93 (m, 3H),
2.62 (t, J = 7.7 Hz, 2H), 2.23 (t, J = 8.0 Hz, 2H), 1.70 – 1.61 (m, 2H), 1.58 – 1.49 (m, 2H).
13
C NMR (100 MHz, CDCl3): 146.2, 142.6, 138.9, 128.3, 128.2, 125.6, 115.6, 113.1, 35.8,
31.4, 31.2, 27.7.
HRMS (CI) Calcd. For C14H18 [M+]: 186.1409, Found: 186.1405.
FTIR (in CDCl3): 3086, 3026, 2932, 2858, 1594, 1496, 1453, 1030, 991, 893, 744, 697 cm-1
.
7 A. Guérinot, S. Reymond and J. Cossy, Angew. Chem. Int. Ed., 2007, 46, 6521. 8 Prepared in accordance with literature procedure: S. M. Smith and J. M. Takacs, J. Am. Chem. Soc., 2010, 132,
1740.
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3-methylenetridec-1-ene (11)
3-methylenetridec-1-ene (11) was prepared by applying a iron catalyzed coupling method
reported by Cossy to a new substrate.9
To a flame dried one neck round bottom flask equipped with a magnetic stir bar was added FeCl3
(0.49 mg, 3.0 mmol, 20 mol%) and THF (50 mL). It was cooled to 0 °C followed by addition of
1-bromodecane (3.3 g, 15 mmol, 1.0 equiv.) The resulting solution was stirred at 0 °C for 10 min
and a solution of chloroprene Grignard2d
(43 mL, 30 mmol, 0.7 M in THF, 2.0 equiv.) and
TMEDA (4.3 mL, 29 mmol, 1.9 equiv.) was added drop wise over 2 h. After further 2 h at 0 °C,
the reaction mixture was quenched by adding an aqueous saturated NH4Cl solution. After
extractive workup and evaporation of the solvent, the residue was distilled (5 Torr, 85 °C) to
furnish the title compound (0.4 g, 14%) as a colorless liquid.
1H NMR (400 MHz, CDCl3): δ 6.37 (dd, J = 17.6, 10.8 Hz, 1H), 5.23 (d, J = 17.5 Hz, 1H),
5.05 (d, J = 10.8 Hz, 1H), 5.01 – 4.97 (m, 2H), 2.20 (t, J = 7.7 Hz, 2H), 1.53 – 1.43 (m, 2H),
1.35 – 1.22 (m, 14H), 0.88 (t, J = 6.8 Hz, 3H).
13C NMR (100 MHz, CDCl3): 146.8, 139.2, 115.5, 113.1, 32.0, 31.5, 29.7, 29.6, 29.4, 28.3,
22.8, 14.2.
Spectral data correspond to that reported in literature.10
9 A. Guérinot, S. Reymond and J. Cossy, Angew. Chem. Int. Ed., 2007, 46, 6521. 10 A. R. Katritzky, L. Serdyuk, D. Toader and X. Wang, J. Org. Chem., 1999, 64, 1888.
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III. Experimental Procedures and Spectroscopic Data for the Nickel
Catalyzed Regioselective Couplings at the C1 – position
General Procedure A for the coupling of 2-substituted dienes 1-11 to paraformaldehyde
An oven dried re-sealable pressure flask equipped with stir bar was charged with Ni(COD)2
(14 mg, 0.050 mmol, 10 mol%), PCy3 (14 mg, 0.050 mmol, 10 mol%), Cs2CO3 (33 mg,
0.100 mmol, 10 mol%) and paraformaldehyde (60 mg, 2.0 mmol, 400 mol%) inside of a drybox.
The flask was sealed and removed from the drybox. Under a flow of argon, toluene was added to
the flask (2 mL, 0.3 M relative to diene). While stirring, the diene (0.5 mmol, 100 mol%) was
added. The flask was sealed and placed in an oil bath at 75 °C for 24 h. The reaction mixture was
allowed to cool to room temperature, at which point methanolic KOH (1.0 M) was added and
stirred for 2 h. CH2Cl2 (30 mL) was added and the mixture was washed with HCl (1.0 M). The
organics were removed and the aqueous layer was extracted twice with CH2Cl2 (15 mL). The
combined organics were dried (Na2SO4), filtered, and evaporated to dryness. The crude residue
was purified by flash column chromatography (SiO2) to furnish the title compounds.
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3-phenylpent-4-en-1-ol (1a)
The reaction was conducted in accordance with General Procedure A (via diene 1). After
heating the reaction for 24 hours and workup, the mixture was purified by flash column
chromatography (SiO2, 20% EtOAc/hexane) to furnish the title compound (58 mg, 72%, 3:1 r.r.)
as a pale yellow oil.
1H NMR (400 MHz, CDCl3): δ 7.35 – 7.27 (m, 2H), 7.24 – 7.18 (m, 3H), 5.98 (ddd, J = 17.4,
10.1, 7.5 Hz, 1H), 5.15 – 5.01 (m, 2H), 3.71 – 3.55 (m, 2H), 3.48 (q, J = 7.6 Hz, 1H), 2.09 – 1.90
(m, 2H), 1.27 (br s, 1H).
13
C NMR (100 MHz, CDCl3): 143.7, 141.8, 128.6, 127.6, 126.4, 114.4, 61.0, 46.3, 38.0.
HRMS (CI) Calcd. For C11H15O [M+H]+: 163.1123, Found: 163.1126.
Spectral data corresponds to that previously reported.11
11 G. Zhang, L. Cui, Y. Wang and L. Zhang, J. Am. Chem. Soc., 2010, 132, 1474.
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3-(4-methylphenyl)pent-4-en-1-ol (2a)
The reaction was conducted in accordance with General Procedure A (via diene 2). After
heating the reaction for 24 hours and workup, the mixture was purified by flash column
chromatography (SiO2, 20% EtOAc/hexane) to furnish the title compound (80 mg, 91%, 3:1 r.r.)
as a colorless oil.
1H NMR (400 MHz, CDCl3): δ 7.16 – 7.07 (m, 4H), 5.96 (ddd, J = 17.5, 10.2, 7.6 Hz, 1H),
5.12 – 5.00 (m, 2H), 3.69 – 3.57 (m, 2H), 3.43 (q, J = 7.6 Hz, 1H), 2.32 (s, 3H),
2.06 – 1.89 (m, 2H), 1.42 (br s, 1H).
13
C NMR (100 MHz, CDCl3): 142.0, 140.6, 135.9, 129.3, 127.4, 114.2, 61.1, 45.9, 38.0, 21.0.
HRMS (CI [NH3]) Calcd. For C12H20NO [M+NH4]+: 194.1545, Found: 194.1541.
FTIR (in CDCl3): 3318, 2924, 2873, 1636, 1513, 1413, 1184, 1109, 1043, 1020, 994, 912, 814,
734 cm-1
.
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3-(4-methoxyphenyl)pent-4-en-1-ol (3a)
The reaction was conducted in accordance with General Procedure A (via diene 3). After
heating the reaction for 24 hours and workup, the mixture was purified by flash column
chromatography (SiO2, 20% EtOAc/hexane) to furnish the title compound (83 mg, 86%, 7:1 r.r.)
as a colorless oil.
1H NMR (400 MHz, CDCl3): δ 7.16 – 7.09 (m, 2H), 6.89 – 6.82 (m, 2H),
5.95 (ddd, J = 17.4, 10.2, 7.5 Hz, 1H), 5.11 – 4.99 (m, 2H), 3.79 (s, 3H), 3.67 – 3.57 (m, 2H),
3.43 (q, J = 7.7 Hz, 1H), 2.06 – 1.87 (m, 2H), 1.51 (br s, J = 7.5 Hz, 1H).
13
C NMR (100 MHz, CDCl3): 142.3, 128.6, 114.2, 114.1, 61.2, 55.4, 45.5, 38.2.
Spectral data corresponds to that previously reported.12
12 O. Muraoka, B.-Z. Zheng, N. Fujiwara and G. Tanabe, J. Chem. Soc., Perkin Trans. 1, 1996, 405.
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3-(3-methoxyphenyl)pent-4-en-1-ol (4a)
The reaction was conducted in accordance with General Procedure A (via diene 4). After
heating the reaction for 24 hours and workup, the mixture was purified by flash column
chromatography (SiO2, 20% EtOAc/hexane) to furnish the title compound (61 mg, 63%, 4:1 r.r.)
as a colorless oil.
1H NMR (400 MHz, CDCl3): δ 7.26 – 7.19 (m, 1H), 6.84 – 6.79 (m, 1H), 6.78 – 6.72 (m, 2H),
5.97 (ddd, J = 17.5, 10.2, 7.6 Hz, 1H), 5.15 – 5.01 (m, 2H), 3.80 (s, 3H), 3.70 – 3.56 (m, 2H),
3.45 (q, J = 7.6 Hz, 1H), 2.12 – 1.85 (m, 2H), 1.31 (br s, 1H).
13
C NMR (100 MHz, CDCl3): 159.8, 145.4, 141.6, 129.6, 119.9, 114.5, 113.5, 111.5, 61.0,
55.2, 46.4, 37.9.
HRMS (EI) Calcd. For C13H19OSi [M]+: 192.1150, Found: 192.1146.
FTIR (in CDCl3): 3338, 2935, 2835, 1599, 1583, 1487, 1453, 1433, 1317, 1259, 1253, 1041,
995, 915, 876, 781, 729, 700 cm-1
.
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3-(2-methoxyphenyl)pent-4-en-1-ol (5a)
In modification to General Procedure A (via diene 5), the reaction was conducted with
20 mol% of Ni(cod)2 and 20 mol% of PCy3. After heating the reaction for 24 hours and workup,
the mixture was purified by flash column chromatography (SiO2, 20% EtOAc/hexane) to furnish
the title compound (55 mg, 57%, 7:1 r.r.) as a colorless oil.
1H NMR (400 MHz, CDCl3): δ 7.26 – 7.10 (m, 2H), 7.00 – 6.84 (m, 2H),
6.06 (ddd, J = 17.3, 10.3, 7.1 Hz, 1H), 5.20 – 5.03 (m, 2H), 4.02 – 3.91 (m, 1H), 3.85 (s, 3H),
3.64 – 3.53 (m, 1H), 3.53 – 3.40 (m, 1H), 2.15 – 2.02 (m, 1H), 1.91 (br s, 1H),
1.88 – 1.76 (m, 1H).
13
C NMR (100 MHz, CDCl3): 156.8, 141.3, 131.7, 128.1, 127.3, 121.0, 114.2, 110.7, 60.9,
55.6, 38.0, 37.6.
HRMS (APCI) Calcd. For C12H16O2 [M]+: 192.1150, Found: 192.1151.
FTIR (in CDCl3): 3350, 3075, 2938, 2836, 1636, 1598, 1585, 1491, 1463, 1438, 1288, 1239,
1181, 1099, 1050, 1028, 913, 791, 751, 672 cm-1
.
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3-(4-fluorophenyl)pent-4-en-1-ol (6a)
The reaction was conducted in accordance with General Procedure A (via diene 6). After
heating the reaction for 24 hours and workup, the mixture was purified by flash column
chromatography (SiO2, 20% EtOAc/hexane) to furnish the title compound (67 mg, 74%, 4:1 r.r.)
as a colorless oil.
1H NMR (400 MHz, CDCl3): δ 7.20 – 7.13 (m, 2H), 7.05 – 6.95 (m, 2H),
5.94 (ddd, J = 17.4, 9.9, 7.5 Hz, 1H), 5.11 – 5.02 (m, 2H), 3.69 – 3.54 (m, 2H),
3.47 (q, J = 7.6 Hz, 1H), 2.05 – 1.85 (m, 2H), 1.41 (br s, 1H).
13
C NMR (100 MHz, CDCl3): 161.4 (d, J = 244.3 Hz), 141.6, 139.3, 128.9 (d, J = 7.8 Hz, 2C),
115.3 (d, J = 21.1 Hz, 2C), 114.6, 60.7, 45.3, 38.0.
19
F NMR (376 MHz, CDCl3): δ -116.9 (mc).
HRMS (CI) Calcd. For C11H12OF [M]+: 180.0950, Found: 180.0949.
FTIR (in CDCl3): 3316, 2937, 1637, 1602, 1508, 1413, 1221, 1159, 1096, 1045, 1015, 916, 832,
741 cm-1
.
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3-cyclohexylpent-4-en-1-ol (7a)
In modification to General Procedure A (via diene 7), the reaction was conducted at 0.3 mmol
scale with 15 mol% of Ni(COD)2 and 15 mol% of PMe3 as ligand. After heating the reaction for
24 hours and workup, the mixture was purified by flash column chromatography (SiO2,
20% EtOAc/hexane) to furnish the title compound (31 mg, 61%, 5.3:1.5:1:1 r.r.) as a colorless
oil.
1H NMR (400 MHz, CDCl3): δ 5.60 (ddd, J = 17.0, 9.9, 9.9 Hz, 1H), 5.07 – 4.90 (m, 2H),
3.69 – 3.54 (m, 2H), 2.01 – 1.87 (m, 1H), 1.79 – 1.43 (m, 8H), 1.31 – 0.84 (m, 5H).
13
C NMR (100 MHz, CDCl3): 141.2, 115.6, 61.7, 47.1, 42.0, 34.6, 31.0, 29.7, 26.7, 26.6.
HRMS (CI) Calcd. For C11H21O [M+H]+: 169.1592, Found: 169.1590.
FTIR (in CDCl3): 3288, 2922, 2852, 2360, 2340, 1448, 1055, 911, 667 cm-1
.
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7-methyl-3-vinyloct-6-en-1-ol (8a)
The reaction was conducted in accordance with General Procedure A (via diene 8). After
heating the reaction for 24 hours and workup, the mixture was purified by flash column
chromatography (SiO2, 20% EtOAc/hexane) to furnish the title compound (57 mg, 68%,
10:1 r.r.) as a colorless oil.
1H NMR (400 MHz, CDCl3): δ 5.57 (mc, 1H), 5.12 – 5.05 (m, 1H), 5.03 (s, 1H),
5.01 – 4.97 (m, 1H), 3.71 – 3.57 (m, 2H), 2.20 – 2.07 (m, 1H), 2.05 – 1.85 (m, 2H),
1.74 – 1.62 (m, 4H), 1.58 (s, 3H), 1.55 – 1.24 (m, 4H).
13
C NMR (100 MHz, CDCl3): 142.7, 131.5, 124.4, 115.0, 61.3, 40.8, 37.8, 35.3, 25.7, 25.6,
17.7.
HRMS (APCI) Calcd. For C11H20O [M+H]+: 169.1587, Found: 169.1588.
FTIR (in CDCl3): 3321, 3076, 2965, 2916, 2856, 1639, 1449, 1419, 1376, 1053, 995, 911, 832,
735, 682 cm-1
.
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Electronic Supplementary Material (ESI) for Chemical ScienceThis journal is © The Royal Society of Chemistry 2013
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7-phenyl-3-vinylheptan-1-ol (9a)
The reaction was conducted in accordance with General Procedure A (via diene 9). After
heating the reaction for 24 hours and workup, the mixture was purified by flash column
chromatography (SiO2, 20% EtOAc/hexane) to furnish the title compound (82 mg, 75%, 7:1 r.r.)
as a colorless oil.
1H NMR (400 MHz, CDCl3): δ 7.32 – 7.25 (m, 2H), 7.22 – 7.15 (m, 3H), 5.64 – 5.49 (m, 1H),
5.05 – 5.01 (m, 1H), 5.01 – 4.97 (m, 1H), 3.71 – 3.58 (m, 2H), 2.67 – 2.55 (m, 2H),
2.19 – 2.05 (m, 1H), 1.76 – 1.25 (m, 9H).
13
C NMR (100 MHz, CDCl3): 142.8, 142.7, 128.3, 128.2, 125.6, 114.8, 61.3, 41.1, 37.8, 35.9,
35.0, 31.5, 26.8.
HRMS (APCI) Calcd. For C15H23O [M+H]+: 219.1743, Found: 219.1744.
FTIR (in CDCl3): 3319, 3063, 3026, 2928, 2856, 1640, 1604, 1496, 1453, 1418, 1050, 1029,
995, 910, 745, 697 cm-1
.
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Electronic Supplementary Material (ESI) for Chemical ScienceThis journal is © The Royal Society of Chemistry 2013
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3-(((triisopropylsilyl)oxy)methyl)pent-4-en-1-ol (10a)
In modification to General Procedure A (via diene 10), the reaction was conducted with
20 mol% of Ni(cod)2 and 20 mol% of PCy3. After heating the reaction for 24 hours and workup,
the mixture was purified by flash column chromatography (SiO2, 20% EtOAc/hexane) to furnish
the title compound (41 mg, 50%, 2:1 r.r (to all other isomers)) as a colorless oil.
1H NMR (400 MHz, CDCl3): δ 5.73 (ddd, J = 17.3, 10.3, 8.4 Hz, 1H), 5.14 – 5.00 (m, 2H),
3.78 – 3.56 (m, 4H), 2.47 – 2.34 (m, 1H), 1.71 – 1.61 (m, 2H), 1.13 – 1.02 (m, 21H).
13
C NMR (100 MHz, CDCl3): 139.7, 115.6, 67.0, 61.3, 44.4, 35.1, 18.0, 18.0, 11.9.
HRMS (CI) Calcd. For C15H33O2Si [M+H]+: 273.2250, Found: 273.2250.
FTIR (in CDCl3): 3345, 2942, 2892, 2865, 1641, 1463, 1383, 1247, 1106, 1055, 1013, 995, 915,
881, 795, 680, 658 cm-1
.
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Electronic Supplementary Material (ESI) for Chemical ScienceThis journal is © The Royal Society of Chemistry 2013
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3-decylpent-4-en-1-ol (11a)
The reaction was conducted in accordance with General Procedure A (via diene 11). After
heating the reaction for 24 hours and workup, the mixture was purified by flash column
chromatography (SiO2, 20% EtOAc/hexane) to furnish the title compound (78 mg, 69%,
11:1 r.r.) as a colorless oil.
1H NMR (400 MHz, CDCl3): δ 5.65 – 5.47 (m, 1H), 5.06 – 4.95 (m, 2H), 3.71 – 3.59 (m, 2H),
2.19 – 2.06 (m, 1H), 1.75 – 1.59 (m, 1H), 1.55 – 1.43 (m, 1H), 1.40 – 1.16 (m, 19H),
0.88 (t, J = 6.9 Hz, 3H).
13
C NMR (100 MHz, CDCl3): 143.0, 114.7, 61.4, 41.2, 37.9, 35.2, 31.9, 29.7, 29.7, 29.6, 29.3,
27.1, 22.7, 14.1.
HRMS (APCI) Calcd. For C15H31O [M+H]+: 227.2369, Found: 227.2373.
FTIR (in CDCl3): 3329, 2922, 2853, 1639, 1465, 1418, 1378, 1051, 995, 911, 721, 682 cm-1
.
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IV. Experimental Procedures and Spectroscopic Data for the Ruthenium
Catalyzed Regioselective Couplings at the C2 – position
General Procedure B for the coupling of 2-substituted dienes 1-11 to paraformaldehyde2c
To a pressure tube equipped with a magnetic stir bar was added RuH2(CO)(PPh3)3 (13.8 mg,
0.015 mmol, 5 mol%) and 1,4-bis(diphenylphosphino)butane (DPPB) (6.4 mg, 0.030 mmol,
5 mol%), and pentadecafluorooctanoic acid (6.2 mg, 0.015 mmol, 5 mol%). Paraformaldehyde
(27.0 mg, 0.60 mmol, 300 mol%) was added. The tube was sealed with a rubber septum, purged
with argon and 2-propanol (0.3 mL, 1.0 M with respect to diene) and diene (0.30 mmol,
100 mol%) were added. The rubber septum was quickly replaced with a screw cap and the
reaction was heated to the indicated temperature for 20 hours. The reaction mixture was
concentrated in vacuo and purified by flash column chromatography (SiO2) under the conditions
noted to furnish the all-carbon quaternary center containing homoallylic alcohols.
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2-methyl-2-phenylbut-3-en-1-ol (1b)
In modification to General Procedure B, the reaction was conducted using 1:1 acetone :
isopropanol [1M] as solvent (via diene 1). After heating the reaction at 80°C for 20 hours, the
mixture was concentrated in vacuo and purified by flash column chromatography (SiO2, 20%
EtOAc/hexane) to furnish the title compound (26.9 mg, 55%, >20:1 r.r., 7:1 (product: over-
reduced product)) as a yellow oil.
1H NMR(400 MHz, CDCl3): δ 7.40 – 7.15 (m, 5H), 6.08 (dd, J = 17.6, 10.8 Hz, 1H),
5.27 (d, J = 10.8 Hz, 1H), 5.16 (d, J = 17.6 Hz, 1H), 3.79 (d, J = 6.4 Hz, 2H), 1.43 (s, 3H),
1.37 (t, J = 6.6 Hz, 1H).
13
C NMR(100 MHz, CDCl3): δ 144.4, 143.5, 128.5, 128.4, 126.9, 126.8, 126.5, 114.6, 69.9,
47.0, 22.6.
Spectral data correspond to that reported in literature.13
13 M.-Y. Ngai, E. Skucas and M. J. Krische, Org. Lett., 2008, 10, 2705.
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2-methyl-2-(p-tolyl)but-3-en-1-ol (3b)
In modification to General Procedure B, the reaction was conducted using 1:1 acetone :
isopropanol [1M] as solvent (via diene 3). After heating the reaction at 80°C for 20 hours, the
mixture was concentrated in vacuo and purified by flash column chromatography (SiO2, 15%
EtOAc/hexane) to furnish the title compound (32.1 mg, 61%, >20:1 r.r.,
4:1 (product: over-reduced product)) as a yellow oil.
1H NMR(400 MHz, CDCl3): δ 7.28 – 7.20 (m, 2H), 7.15 (d, J = 8.0 Hz, 2H),
6.06 (dd, J = 17.6, 10.8 Hz, 1H), 5.25 (dd, J = 10.8, 1.2 Hz, 1H), 5.14 (dd, J = 17.6, 1.2 Hz, 1H),
3.80 – 3.72 (m, 2H), 2.33 (s, 3H), 1.44 – 1.35 (m, 4H).
13
C NMR(100 MHz, CDCl3): δ 143.7, 141.4, 136.1, 129.2, 126.7, 114.4, 70.0, 46.6, 22.6, 20.9.
HRMS (CI) Calcd. For C12H16O [M]+: 176.1201, Found: 176.1201.
FTIR (in CDCl3): 3385, 2967, 2923, 2876, 1634, 1513, 1454, 1412, 1378, 1192, 1116, 1037,
1017, 914, 814, 756, 725 cm-1
.
Spectral data correspond to that reported in literature.14
14 Q. Zhang, S.-F. Zhu, Y. Cai, L.-X. Wang and Q.-L. Zhou, Sci. China Chem., 2010, 53, 1899.
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2-(4-fluorophenyl)-2-methylbut-3-en-1-ol (6b)
In modification to General Procedure B, the reaction was conducted using 1:1 acetone :
isopropanol [1M] as solvent (via diene 6). After heating the reaction at 80°C for 20 hours, the
mixture was concentrated in vacuo and purified by flash column chromatography (SiO2, 20%
EtOAc/hexane) to furnish the title compound (35.3 mg, 65%, >20:1 r.r., 8:1 (product: over-
reduced product)) as a yellow oil.
1H NMR(400 MHz, CDCl3): δ 7.36 – 7.29 (m, 2H), 7.06 – 6.98 (m, 2H),
6.04 (dd, J = 17.6, 10.8 Hz, 1H), 5.27 (dd, J = 10.8, 1.1 Hz, 1H), 5.14 (dd, J = 17.6, 1.1 Hz, 1H),
3.76 (d, J = 6.4 Hz, 2H), 1.45 – 1.36 (m, 4H).
13
C NMR(100 MHz, CDCl3): δ 161.4 (d, J = 245.4 Hz), 143.4, 140.1 (d, J = 3.0 Hz),
128.5 (d, J = 7.8 Hz), 115.1 (d, J = 20.9 Hz), 114.8, 69.9, 46.5, 22.8.
19
F NMR(376 MHz, CDCl3): δ -116.67 – -116.90 (m).
Spectral data correspond to that reported in literature.13
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2-methyl-6-phenyl-2-vinylhexan-1-ol (9b)
The reaction was conducted in accordance with General Procedure B (via diene 9). After
heating the reaction at 90°C for 20 hours, the mixture was concentrated in vacuo and purified by
flash column chromatography (SiO2, 20% EtOAc/hexane) to furnish the title compound
(41.4 mg, 63%, >8:1 r.r.) as a colorless oil.
1H NMR(400 MHz, CDCl3): δ 7.31 – 7.23 (m, 2H), 7.20 – 7.12 (m, 3H),
5.70 (dd, J = 17.6, 10.9 Hz, 1H), 5.16 (dd, J = 10.9, 1.3 Hz, 1H), 5.04 (dd, J = 17.6, 1.3 Hz, 1H),
3.43 – 3.27 (m, 2H), 2.66 – 2.53 (m, 2H), 1.65 – 1.53 (m, 2H), 1.40 – 1.21 (m, 5H), 1.00 (s, 3H).
13
C NMR(100 MHz, CDCl3): δ 144.1, 142.7, 128.3, 128.2, 125.6, 114.6, 70.2, 42.3, 37.0, 35.9,
32.3, 23.5, 19.6.
HRMS (CI) Calcd. For C15H22O [M]+: 218.1671, Found: 218.1169.
FTIR (in CDCl3): 3394, 2933, 2859, 1639, 1603, 1496, 1453, 1414, 1373, 1217, 1030, 908, 755,
731, 698 cm-1
.
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2-methyl-2-vinyldodecan-1-ol (11b)
The reaction was conducted in accordance with General Procedure B (via diene 11). After
heating the reaction at 90°C for 20 hours, the mixture was concentrated in vacuo and purified by
flash column chromatography (SiO2, 20% EtOAc/hexane) to furnish the title compound
(39.0 mg, 57%, 8:1 r.r.) as a colorless oil.
1H NMR(400 MHz, CDCl3): δ 5.70 (dd, J = 17.6, 10.9 Hz, 1H), 5.16 (dd, J = 10.9, 1.4 Hz, 1H),
5.04 (dd, J = 17.6, 1.4 Hz, 1H), 3.35 (qd, J = 10.6, 6.3 Hz, 2H), 1.38 – 1.13 (m, 19H),
1.00 (s, 3H), 0.88 (t, J = 6.9 Hz, 3H).
13
C NMR(100 MHz, CDCl3): δ 144.3, 114.5, 70.2, 42.3, 37.2, 31.9, 30.5, 29.7, 29.6, 29.3, 23.76,
22.7, 19.6, 14.1.
HRMS (CI) Calcd. For C15H31O [M+H]+: 227.2375, Found:227.2378.
FTIR (in CDCl3): 3372, 2924, 2853, 1639, 1466, 1414, 1377, 1215, 1035, 909, 759, 734 cm-1
.
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V. Experimental Procedures and Spectroscopic Data for the Ruthenium
Catalyzed Regioselective Couplings at the C3 – position
General Procedure C for the coupling of 2-substituted dienes 1-11 to paraformaldehyde
To a pressure tube equipped with magnetic stir bar was added RuHCl(CO)(PPh3)3 (14.1 mg,
0.015 mmol, 5 mol%) and 1,4-bis(diphenylphosphino)butane (DPPB) (6.4 mg, 0.030 mmol,
5 mol%). Paraformaldehyde (18.0 mg, 0.60 mmol, 200 mol%) was added. The tube was sealed
with a rubber septum, purged with argon and 1,4-dioxane (0.15 mL, 2.0 M with respect to diene),
diene (0.30 mmol, 100 mol%) and 2-propanol (0.11 mL, 1.5 mmol, 500 mol%) were added. The
rubber septum was quickly replaced with a screw cap and the reaction was heated to the
indicated temperature for 24 hours. The reaction mixture was concentrated in vacuo and purified
by flash column chromatography (SiO2) under the conditions noted to furnish the homoallylic
alcohols.
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2-methyl-3-phenylbut-3-en-1-ol (1c)
The reaction was conducted in accordance with General Procedure C (via diene 1). After
heating the reaction at 115°C for 24 hours, the mixture was concentrated in vacuo and purified
by flash column chromatography (SiO2, 15% EtOAc/hexane) to furnish the title compound
(31.6 mg, 65%, >20:1 r.r.) as a yellow oil.
1H NMR(400 MHz, CDCl3): δ 7.38 – 7.26 (m, 5H), 5.34 (d, J = 1.0 Hz, 1H),
5.13 (t, J = 1.1 Hz, 1H), 3.66 (dd, J = 10.7, 6.0 Hz, 1H), 3.54 (dd, J = 10.7, 5.9 Hz, 1H),
3.01 – 2.89 (m, 1H), 1.52 (s, 1H), 1.19 (d, J = 6.9 Hz, 3H).
13
C NMR(100 MHz, CDCl3): δ151.2, 142.13, 128.3, 127.5, 126.6, 112.8, 66.5, 40.8, 16.7.
HRMS (CI) Calcd. For C11H14O [M]+: 162.1045, Found: 162.1044.
FTIR (neat): 3349, 3056, 2964, 2928, 2875, 1625, 1600, 1574, 1493, 1453, 1261, 1025, 979,
899, 777, 700 cm-1
.
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Electronic Supplementary Material (ESI) for Chemical ScienceThis journal is © The Royal Society of Chemistry 2013
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2-methyl-3-(4-methyl)but-3-en-1-ol (2c)
The reaction was conducted in accordance with General Procedure C (via diene 2). After
heating the reaction at 95°C for 24 hours, the mixture was concentrated in vacuo and purified by
flash column chromatography (SiO2, 15% EtOAc/hexane) to furnish the title compound
(36.8 mg, 70%, >20:1 r.r.) as a yellow oil.
1H NMR(400 MHz, CDCl3): δ 7.28 – 7.23 (m, 2H), 7.13 (dd, J = 8.4, 0.5 Hz, 2H),
5.30 (d, J = 1.0 Hz, 1H), 5.07 (t, J = 1.1 Hz, 1H), 3.71 – 3.58 (m, 1H), 3.57 – 3.46 (m, 1H),
2.98 – 2.87 (m, 1H), 2.34 (s, 3H), 1.53 (t, J = 5.0 Hz, 1H), 1.17 (d, J = 6.9 Hz, 3H).
13
C NMR(100 MHz, CDCl3): δ151.0, 139.1, 137.2, 129.0, 126.4, 112.1, 66.5, 40.7, 21.1, 16.7.
HRMS (CI) Calcd. For C12H16O [M]+: 176.1201, Found: 176.1198.
FTIR (neat): 3332, 2963, 2923, 2874, 1623, 1511, 1454, 1403, 1213, 1117, 1027, 979, 896, 823,
734 cm-1
.
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3-(4-methoxyphenyl)-2-methylbut-3-en-1-ol (3c)
The reaction was conducted in accordance with General Procedure C (via diene 3). After
heating the reaction at 95°C for 24 hours, the mixture was concentrated in vacuo and purified by
flash column chromatography (SiO2, 20% EtOAc/hexane) to furnish the title compound
(40.6 mg, 70%, >20:1 r.r.) as a yellow oil.
1H NMR(400 MHz, CDCl3): δ 7.34 – 7.28 (m, 2H), 6.90 – 6.84 (m, 2H),
5.29 (d, J = 0.9 Hz, 1H), 5.04 (s, 1H), 3.81 (s, 3H), 3.70 – 3.60 (m, 1H), 3.59 – 3.48 (m, 1H),
2.98 – 2.87 (m, 1H), 1.46 (t, J = 6.1 Hz, 1H), 1.17 (d, J = 6.9 Hz, 3H).
13
C NMR(100 MHz, CDCl3): δ159.1, 150.5, 134.4, 127.6, 113.7, 111.5, 66.5, 55.3, 40.1, 16.8.
FTIR (neat): 3385, 2961, 2932, 2836, 1607, 1573, 1509, 1462, 1411, 1292, 1179, 1114, 1028,
978, 896, 804, 734, 696 cm-1
.
Spectral data correspond to that reported in literature.15
15 S. Kano, Y. Yuasa, K. Asami and S. Shibuya, Heterocycles, 1988, 27, 1437.
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3-(3-methoxyphenyl)-2-methylbut-3-en-1-ol (4c)
The reaction was conducted in accordance with General Procedure C (via diene 4). After
heating the reaction at 95°C for 24 hours, the mixture was concentrated in vacuo and purified by
flash column chromatography (SiO2, 25% EtOAc/hexane) to furnish the title compound
(41.4 mg, 72%, >20:1 r.r.) as a yellow oil.
1H NMR(400 MHz, CDCl3): δ 7.28 – 7.21 (m, 1H), 6.98 – 6.87 (m, 2H),
6.83 (ddd, J = 8.2, 2.6, 0.8 Hz, 1H), 5.33 (d, J = 0.9 Hz, 1H), 5.11 (s, 1H), 3.81 (s, 3H),
3.70 – 3.61 (m, 1H), 3.58 – 3.46 (m, 1H), 2.97 – 2.85 (m, 1H), 1.52 (s, 1H),
1.17 (d, J = 6.9 Hz, 3H).
13
C NMR(100 MHz, CDCl3): δ 159.5, 151.1, 143.7, 129.3, 119.1, 112.9, 112.6, 112.6, 66.5,
55.2, 40.8, 16.7.
FTIR (neat): 3361, 2962, 2876, 2834, 1597, 1575, 1487, 1463, 1428, 1317, 1286, 1219, 1180,
1114, 1028, 978, 907, 881, 782, 729 cm-1
.
Spectral data correspond to that reported in literature.15
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3-(2-methoxyphenyl)-2-methylbut-3-en-1-ol (5c)
The reaction was conducted in accordance with General Procedure C (via diene 5). After
heating the reaction at 95°C for 24 hours, the mixture was concentrated in vacuo and purified by
flash column chromatography (SiO2, 20% EtOAc/hexane) to furnish the title compound
(40.6 mg, 70%, >20:1 r.r.) as a yellow oil.
1H NMR(400 MHz, CDCl3): δ 7.30 – 7.24 (m, 1H), 7.06 (dd, J = 7.4, 1.8 Hz, 1H),
6.97 – 6.87 (m, 2H), 5.32 – 5.26 (m, 1H), 5.08 (d, J = 1.7 Hz, 1H), 3.82 (s, 3H),
3.51 – 3.37 (m, 2H), 2.83 – 2.71 (m, 1H), 2.30 – 2.22 (m, 1H), 1.08 (d, J = 7.0 Hz, 3H).
13
C NMR(100 MHz, CDCl3): δ 156.2, 149.0, 131.3, 130.5, 128.5, 120.6, 115.9, 110.6, 65.9,
55.5, 43.2, 16.1.
HRMS (CI) Calcd.For C12H16O2 [M]+: 192.1150, Found: 192.1152.
FTIR (neat): 3393, 2961, 2835, 1630, 1597, 1578, 1489, 1455, 1435, 1291, 1238, 1180, 1161,
1107, 1078, 1025, 978, 905, 846, 804, 751, 733 cm-1
.
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3-(4-fluorophenyl)-2-methylbut-3-en-1-ol (6c)
The reaction was conducted in accordance with General Procedure C (via diene 6). After
heating the reaction at 115°C for 24 hours, the mixture was concentrated in vacuo and purified
by flash column chromatography (SiO2, 20% EtOAc/hexane) to furnish the title compound
(35.1 mg, 65%, >20:1 r.r.) as a yellow oil.
1H NMR(400 MHz, CDCl3): δ 7.36 – 7.27 (m, 2H), 7.06 – 6.97 (m, 2H),
5.29 (d, J = 0.8 Hz, 1H), 5.11 (t, J = 0.9 Hz, 1H), 3.65 (dd, J = 10.7, 6.1 Hz, 1H),
3.53 (dd, J = 10.7, 5.9 Hz, 1H), 2.94 – 2.83 (m, 1H), 1.45 (s, 1H), 1.16 (d, J = 6.9 Hz, 3H).
13
C NMR(100 MHz, CDCl3): δ 162.3 (d, J = 246.2 Hz), 150.3, 138.1 (d, J = 3.2 Hz),
128.2 (d, J = 7.9 Hz), 115.1 (d, J = 21.3 Hz), 112.9, 66.4, 40.9, 16.7.
19
F NMR (376 MHz, CDCl3): δ -115.16 – -115.38 (m).
HRMS (CI) Calcd. For C11H13OF [M]+: 180.0950, Found: 180.0950.
FTIR (in CDCl3): 3346, 2964, 2929, 1625, 1602, 1508, 1456, 1401, 1223, 1160, 1098, 1027,
979, 904, 839, 816, 735, 696 cm-1
.
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Electronic Supplementary Material (ESI) for Chemical ScienceThis journal is © The Royal Society of Chemistry 2013
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3-cyclohexyl-2-methylbut-3-en-1-ol (7c)
The reaction was conducted in accordance with General Procedure C (via diene 7). After
heating the reaction at 95°C for 24 hours, the mixture was concentrated in vacuo and purified by
flash column chromatography (SiO2, 10% EtOAc/hexane) to furnish the title compound
(40.9 mg, 81%, 8:1 r.r.) as a yellow oil.
1H NMR(400 MHz, CDCl3): δ 4.90 (s, 1H), 4.79 (s, 1H), 3.60 – 3.45 (m, 2H),
2.42 – 2.30 (m, 1H), 1.89 – 1.56 (m, 6H), 1.48 (t, J = 6.1 Hz, 1H), 1.38 – 1.08 (m, 5H),
1.04 (d, J = 6.9 Hz, 3H).
13
C NMR(100 MHz, CDCl3): δ 157.4, 107.7, 66.4, 43.9, 41.4, 33.2, 33.0, 26.9, 26.8, 26.3, 17.3.
HRMS (CI) Calcd. For C11H21O [M+H]+: 169.1592, Found: 169.1594.
FTIR (neat): 3362, 2924, 2852, 1639, 1448, 1025, 980, 886, 844, 734, 697 cm-1
.
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2,7-dimethyl-3-methyleneoct-6-en-1-ol (8c)
The reaction was conducted in accordance with General Procedure C (via diene 8). After
heating the reaction at 115°C for 24 hours, the mixture was concentrated in vacuo and purified
by flash column chromatography (SiO2, 15% EtOAc/hexane) to furnish the title compound
(30.8 mg, 61%, >20:1 r.r.) as a colorless oil.
1H NMR(400 MHz, CDCl3): δ 5.14-5.10 (m, 1H), 4.93 – 4.89 (m, 1H), 4.87 – 4.83 (m, 1H),
3.61 – 3.43 (m, 2H), 2.45 – 2.30 (m, 1H), 2.19 – 2.08 (m, 2H), 2.08 – 1.98 (m, 2H),
1.69 (d, J = 1.1 Hz, 3H), 1.66 – 1.58 (m, 3H), 1.45 (s, 1H), 1.05 (d, J = 7.0 Hz, 3H).
13
C NMR(100 MHz, CDCl3): δ 150.9, 131.9, 123.9, 110.0, 65.8, 42.5, 34.0, 26.5, 16.2.
HRMS (CI) Calcd. For C11H19O [M-H]+: 167.1436, Found: 167.1434.
FTIR (neat): 3329, 3076, 2966, 2924, 2876, 1642, 1452, 1376, 1220, 1107, 1028, 981, 891, 831,
734 cm-1
.
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2-methyl-3-methylene-7-phenylheptan-1-ol (9c)
The reaction was conducted in accordance with General Procedure C (via diene 9). After
heating the reaction at 115°C for 24 hours, the mixture was concentrated in vacuo and purified
by flash column chromatography (SiO2, 20% EtOAc/hexane) to furnish the title compound
(43.9 mg, 67%, 17:1 r.r.) as a yellow oil.
1H NMR(400 MHz, CDCl3): δ 7.32 – 7.25 (m, 2H), 7.22 – 7.15 (m, 3H), 4.91 – 4.87 (m, 1H),
4.84 (s, 1H), 3.60 – 3.45 (m, 2H), 2.68 – 2.59 (m, 2H), 2.41 – 2.29 (m, 1H), 2.13 – 1.96 (m, 2H),
1.71 – 1.59 (m, 2H), 1.58 – 1.47 (m, 2H), 1.42 (s, 1H), 1.04 (d, J = 7.0 Hz, 3H).
13
C NMR(100 MHz, CDCl3): δ 151.1, 142.5, 128.4, 128.3, 125.7, 109.8, 65.9, 42.2, 35.8, 34.2,
31.2, 27.5, 16.3.
HRMS (CI) Calcd. For C15H22O [M]+: 218.1671, Found: 218.1672.
FTIR (neat): 3355, 3026, 2931, 2858, 1641, 1603, 1496, 1453, 1028, 979, 908, 890, 732,
698 cm-1
.
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2-methyl-3-(((triisopropylsilyl)oxy)methyl)but-3-en-1-ol (10c)
The reaction was conducted in accordance with General Procedure C (via diene 10). After
heating the reaction at 95°C for 24 hours, the mixture was concentrated in vacuo and purified by
flash column chromatography (SiO2, 10% EtOAc/hexane) to furnish the title compound
(66.0 mg, 81%, >20:1 r.r.) as a yellow oil.
1H NMR(400 MHz, CDCl3): δ 5.19 (q, J = 1.5 Hz, 1H), 4.96 (dd, J = 1.6, 0.8 Hz, 1H),
4.26 – 4.10 (m, 2H), 3.63 – 3.47 (m, 2H), 2.49 – 2.35 (m, 2H), 1.18 – 1.02 (m, 24H).
13
C NMR(100 MHz, CDCl3): δ 150.3, 111.6, 66.9, 65.6, 40.1, 18.0, 16.3, 11.9.
HRMS (CI) Calcd. For C15H33O2Si [M+H]+: 273.2250, Found: 273.2253.
FTIR (neat): 3348, 2942, 2866, 1650, 1463, 1385, 1247, 1087, 1060, 1031, 996, 899, 881, 817,
792, 734, 681, 658 cm-1
.
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2-methyl-3-methylenetridecan-1-ol (11c)
The reaction was conducted in accordance with General Procedure C (via diene 11). After
heating the reaction at 115°C for 24 hours, the mixture was concentrated in vacuo and purified
by flash column chromatography (SiO2, 20% EtOAc/hexane) to furnish the title compound
(42.1 mg, 62%, >20:1 r.r.) as a yellow oil.
1H NMR(400 MHz, CDCl3): δ 4.89 (q, J = 1.4 Hz, 1H), 4.83 (dd, J = 1.4, 0.8 Hz, 1H),
3.58 – 3.46 (m, 2H), 2.41 – 2.31 (m, 1H), 2.06 – 1.94 (m, 2H), 1.50 – 1.37 (m, 1H), 1.36 – 1.17
(m, 16H), 1.04 (d, J = 7.0 Hz, 3H), 0.88 (t, J = 6.9 Hz, 3H).
13
C NMR(100 MHz, CDCl3): δ 151.4, 109.7, 65.8, 42.3, 34.3, 31.9, 29.6 (s, 2C), 29.6, 29.5,
29.3, 28.0, 22.7, 16.3, 14.1.
HRMS (CI) Calcd. For C15H31O [M+H]+: 227.2375, Found: 227.2373.
FTIR (neat): 3362, 2957, 2923, 2853, 1642, 1464, 1377, 1028, 980, 907, 890, 734 cm-1
.
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VI. Experimental Procedures and Spectroscopic Data for the Nickel
Catalyzed Regioselective Couplings at the C4 – position
General Procedure D for the coupling of 2-substituted dienes 12-13 to paraformaldehyde
An oven dried re-sealable pressure flask equipped with stir bar was charged with Ni(COD)2
(28 mg, 0.10 mmol, 20 mol%), PCy3 (28 mg, 0.10 mmol, 20 mol%) and paraformaldehyde
(60 mg, 2.0 mmol, 400 mol%) inside of a drybox. The flask was sealed and removed from the
drybox. Under a flow of argon, toluene was added to the flask (2 mL, 0.25 M relative to diene).
While stirring, the diene (0.5 mmol, 100 mol%) was added. The flask was sealed and placed in
an oil bath at 60 °C for 24 h. The reaction mixture was allowed to cool to room temperature, at
which point methanolic KOH (1.0 M) was added and stirred for 2 h. CH2Cl2 (30 mL) was added
and the mixture was washed with HCl (1.0 M). The organics were removed and the aqueous
layer was extracted twice with CH2Cl2 (15 mL). The combined organics were dried (Na2SO4),
filtered, and evaporated to dryness. The crude residue was purified by flash column
chromatography (SiO2) to furnish the title compounds.
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4-(dimethyl(phenyl)silyl)pent-4-en-1-ol (12d)
The reaction was conducted in accordance with General Procedure D (via diene 12). After
heating the reaction for 24 hours and workup, the mixture was purified by flash column
chromatography (SiO2, DCM) to furnish the title compound (78 mg, 71%, 7:1 r.r.) as a colorless
oil.
1H NMR (400 MHz, CDCl3): δ 7.56 – 7.48 (m, 2H), 7.40 – 7.32 (m, 3H), 5.78 – 5.67 (m, 1H),
5.51 – 5.37 (m, 1H), 3.56 (t, J = 6.5 Hz, 2H), 2.19 (t, J = 7.7 Hz, 2H), 1.70 – 1.53 (m, 2H),
0.39 (s, 6H).
13
C NMR (100 MHz, CDCl3): 149.7, 138.1, 133.9, 129.0, 127.8, 127.8, 126.1, 62.6, 31.9, 31.7,
-3.0.
HRMS (CI) Calcd. For C13H19OSi [M-H]+: 219.1205, Found: 219.1208.
FTIR (in CDCl3): 3334, 3050, 2941, 1625, 1427, 1248, 1111, 1055, 924, 832, 816, 774, 730,
699, 668 cm-1
.
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4-(dimethyl(benzyl)silyl)pent-4-en-1-ol (13d)
The reaction was conducted in accordance with General Procedure D (via diene 13). After
heating the reaction for 24 hours and workup, the mixture was purified by flash column
chromatography (SiO2, DCM) to furnish the title compound (82 mg, 70%, 7:1 r.r.) as a colorless
oil.
1H NMR (400 MHz, CDCl3): δ 7.23 – 7.17 (m, 2H), 7.07 (app. t, J = 7.4 Hz, 1H), 7.02 – 6.97
(m, 2H), 5.64 (dt, J = 2.9, 1.6 Hz, 1H), 5.36 – 5.33 (m, 1H), 3.64 (t, J = 6.5 Hz, 2H), 2.21 – 2.09
(m, 4H), 1.73 – 1.62 (m, 2H), 1.26 (br s, 1H), 0.07 (s, 6H).
13
C NMR (100 MHz, CDCl3): 150.1, 140.0, 128.3, 128.3, 128.2, 125.4, 124.1, 62.8, 32.1, 31.9,
25.6, -3.5.
HRMS (APCI) Calcd. For C14H23OSi [M-H]+: 235.1518, Found: 235.1517.
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4-(tributylstannyl)pent-4-en-1-ol (14d)
In modification to General Procedure D (via diene 14), the reaction was conducted at 75 °C.
After heating the reaction for 24 hours and workup, the mixture was purified by flash column
chromatography (SiO2, DCM) to furnish the title compound (105 mg, 56%, >20:1 r.r.) as a
colorless oil.
1H NMR (400 MHz, CDCl3): δ 5.71 (dt, J = 2.8, 1.5 Hz, and JSn-H = 68.7 Hz, 1H), 5.14 (mc, 1H),
3.65 (dd, J = 6.3, 4.5 Hz, and JSn-H = 31.4 Hz, 2H), 2.33 (t, J = 7.6 Hz, 2H), 1.65 (mc, 2H), 1.57 –
1.42 (m, 6H), 1.40 – 1.21 (m, 6H), 0.99 – 0.81 (m, 15H).
13
C NMR (100 MHz, CDCl3): δ 155.0, 125.3, 62.8, 37.5, 32.5, 29.2, 27.5, 13.8, 9.7.
HRMS (CI) Calcd. For C17H36OClSn [M+Cl]−: 411.1477, Found: 411.1487.
Spectral data correspond to that reported in literature.16
16
A. Barbero, P. Cuadrado, I. Fleming, A. M. González and F. J. Pulido, J. Chem. Soc. Perkin Trans. 1, 1992, 327.
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VII. Experimental Procedure and Spectroscopic Data for the Hiyama
Coupling of the C4 Product.
4-phenylpent-4-en-1-ol (12e)
The reaction was conducted by modifying a literature procedure by Denmark.17
To a dry Schlenk tube with a stir bar was added a solution of 4-(dimethyl(phenyl)silyl)pent-4-en-
1-ol (12d) (77 mg, 0.33 mmol) in THF (0.66ml) under an argon atmosphere. To this was added
iodobenzene (67 mg, 0.33 mmol, 1.0 equiv.) and then TBAF (0.66 ml, 1.0 M in THF, 2.0
equiv.). The resulting solution was stirred at room temperature for 5 min. Pd(dba)2 (9.5 mg,
0.017 mmol, 5 mol%) was added. The reaction mixture was stirred at room temperature for
30 min. After filtering through silica gel and washing with DCM, the solvents were removed
under reduced pressure. The mixture was purified by flash column chromatography (SiO2, DCM)
to furnish the title compound (42 mg, 78%) as a colorless oil.
1H NMR (400 MHz, CDCl3): δ 7.45 – 7.23 (m, 5H), 5.30 (s, 1H), 5.10 (d, J = 1.2 Hz, 1H), 3.67
(t, J = 5.5 Hz, 2H), 2.61 (t, J = 7.5 Hz, 2H), 1.80 – 1.67 (m, 2H), 1.26 (br s, 1H).
13
C NMR (100 MHz, CDCl3): 148.1, 141.1, 128.4, 127.5, 126.2, 112.7, 62.6, 31.7, 31.3.
Spectral data correspond to that reported in literature.18
17
S. E. Denmark and S. A. Tymonko, J. Am. Chem. Soc., 2005, 127, 8004. 18
A. Takemiya and J. F. Hartwig, J. Am. Chem. Soc., 2006, 128, 6042.
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VIII. Deuterium Labeling of Nickel Catalyzed Coupling at the C1-position
(CD2O)n
Ha 0% 2H
Hb 100% 2H
Hc 0% 2H
Hd 0% 2H
He 0% 2H
Hf 100% 2H
Yield 65% (6:1 r.r.)
The above values represent the average of two trials. The extent of deuterium incorporation was
determined for the major regioisomer (alcohol 3a).
Diene 3 was subjected to one experiment employing deuterio-paraformaldehyde under otherwise
the same conditions to furnish 3-(4-methoxyphenyl)pent-4-en-1-ol (3a). The extent of deuterium
incorporation was determined in the isolated product
deuterio-3-(4-methoxyphenyl)pent-4-en-1-ol by integration of the corresponding signals in 1H NMR (400 MHz, CDCl3) and
2H NMR (77 MHz, CHCl3).
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Experiment 1.
(*Inseparable regioisomer)
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IX. Deuterium Labeling of Ruthenium Catalyzed Coupling at the C3-position
(CD2O)n + i-PrOH (CH2O)n + i-PrOH-d8 (CD2O)n + i-PrOH-d8
Ha 0% 2H
6% 2H
0% 2H
Hb 0% 2H
5%
2H
2%
2H
Hc 25% 2H
12% 2H
31% 2H
Hd 13% 2H
8% 2H
17% 2H
He 100% 2H
1% 2H
100% 2H
Yield 65% (20:1 r.r.) 60% (12:1 r.r.) 64% (17:1 r.r)
The above values represent the average of two trials. The extent of deuterium incorporation was
determined for the major regioisomer (alcohol 3c).
Diene 3 was subjected to three separate experiments employing deuterio-paraformaldehyde,
d8-isopropanol, and both deuterio-paraformaldehyde and d8-isopropanol under otherwise the
same conditions to furnish 3-(4-methoxyphenyl)-2-methylbut-3-en-1-ol (3c). The extent of
deuterium incorporation was determined in the isolated product
deuterio-3-(4-methoxyphenyl)-2-methylbut-3-en-1-ol by integration of the corresponding
signals in 1H NMR (400 MHz, CDCl3) and
2H NMR (77 MHz, CHCl3).
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Experiment 1.
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Experiment 2.
(*Inseparable regioisomer)
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Experiment 3.
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